|Publication number||US7042565 B2|
|Application number||US 10/777,720|
|Publication date||May 9, 2006|
|Filing date||Feb 13, 2004|
|Priority date||Feb 13, 2004|
|Also published as||US20050179894|
|Publication number||10777720, 777720, US 7042565 B2, US 7042565B2, US-B2-7042565, US7042565 B2, US7042565B2|
|Inventors||Jiann-Hua Wang, Hui Ju Chen, Tzu-Chiang Wu, Chien-Ho Chuang, Tsung-Kai Chuang|
|Original Assignee||Kaiwood Technology Co., Ltd.|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (3), Referenced by (6), Classifications (6), Legal Events (5)|
|External Links: USPTO, USPTO Assignment, Espacenet|
1. Field of the Invention
The present invention relates to a fluorescent microarray analyzer, particularly to a fluorescent microarray analyzer for detecting fluorescent signals emitting from a biochip by means of spectrum analysis.
2. The Prior Arts
As “working draft” of the human sequence unraveled by the Human Genome Project published in Nature (15 Feb., 2001), simultaneously with a companion publication of the human sequence generated by Celera Genomics Corporation (Science, 16 Feb., 2001), understanding the physical functions and the mechanisms of human genes becomes the next important goal in the field. To accelerate the progress of the related research, high-throughput tools for efficient analysis are available. Biochip, results of mass of samples expressed on surface of a small solid carrier, is such a useful analytic tool. Biochip can be employed in gene expression, drug selection and disease diagnosis in both basic research and clinical application fields.
Three kinds of biochips are known, namely DNA chip, lab-on-a-chip and protein chip. Since the protein chip and the lab-on-a-chip are difficult to operate, the DNA chip is in common use now. The detection of the DNA chip is shown in
Cyanine 3 (Cy3) and cyanine 5 (Cy5) are two fluorophores in common use. Cy3, with peak absorption at 550 nm, is generally excited with a laser beam of 532 nm and emitting fluorescence which has central wavelength at 570 nm. Cy5, with peak absorption at 649 nm, is generally excited with laser beams of 632.8 nm or 635 nm and emitting fluorescence which has central wavelength at 678 nm. Filters are generally used to eliminate the interference caused by the original beams of light from the light source and the scattering light from the slide. When filtering out the interfering light from the light source, some signals of the resulting fluorescence may be filtered out at the same time due to the crosstalk between the fluorescence and the interfering light. In addition, problems of exchanging filters happens when two or more fluorophores are used on the same biochip.
A primary object of the present invention is to provide a fluorescent microarray analyzer in which the photomultiplier tube of the conventional biochip scanner device is replaced with a spectrophotometer. Therefore, accurate signals of fluorescence are obtained, and there is no need to set a filter.
A second object of the invention is to provide a fluorescent microarray analyzer that allows for real-time analysis without scanning all samples on the biochip. As a result, a lot of time taken for analysis is saved.
A third object of the invention is to provide a fluorescent microarray analyzer that reads signals from spectrophotometer directly without conversion into image data and thus eliminating errors occurring during the conversion.
In order to realize the foregoing objects, a fluorescent microarray analyzer of the present invention comprises: a light source for emitting light beam; a light processing unit for focusing the beams on the biochip and exciting fluorescent targets on the biochip to produce fluorescence; a focusing lens for focusing the fluorescence on a spectrophotometer, which detects the fluorescence; and an output device for outputting/displaying the signal detected by the spectrophotometer. The resulting signal of the output device is not a converted image data. The light processing unit comprises: a beam splitter for reflecting the light beam to pass through a focusing lens which focuses the light beam on the biochip and exciting fluorescent targets on the biochip to produce fluorescence which passes through the beam splitter and the focus lens to the spectrometer. Another focusing lens may be set between the light source and the beam splitter to enhance the focusing effect.
Furthermore, if desired, image data can be produced by conversion from the signals detected by the spectrophotometer. The image data are used for showing the positions of DNA spots on a biochip. The signal intensity of each sample comes from the signals detected by the spectrophotometer and therefore no errors arise as what happened in the process of converting an electrical signal into an image data in the conventional biochips.
The resulting signals of fluorescence are obtained by the spectrophotometer of the present invention. A real-time analysis proceeds while samples on the biochip are being scanned. As signals of different wavelength can be shown by the spectrophotometer, a more accurate result of signals of fluorescence form samples is obtained without a filter. In addition, more accurate results are produced even more than two fluorophores are used on the same biochip.
For more detailed information regarding advantages and features of the present invention, examples of preferred embodiments will be described below with reference to the annexed drawings. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as claimed.
The related drawings in connection with the detailed description of the present invention to be made later are described briefly as follows, in which:
Preferred embodiments of the present invention will now be described in detail below with reference to the accompanying drawings.
A biochip is placed on a platform (59) first when analyzed by the fluorescent microarray analyzer of the present invention. The platform (59) is movable in two different directions, for example X and Y directions that are orthogonal, under the control of a computer (58). When scanning, the light beam from laser source (50) passes through the focusing lens (51) and reaches a surface of the biochip (54). Fluorescence (55) is excited from fluorescent targets on the biochip (54). The fluorescence (55) passes through the focusing lens (53), the beam splitter (52) and the focusing lens (56) to focus on the spectrophotometer (57). The signal of fluorescence is detected by the spectrophotometer (57) and transmitted to an output device (58). The signal is output/displayed directly by the output device (58). For the convenience of analysis, the output device (58) may comprise a computer, which is loaded with a algorithm to control the movement of the platform (59) so that operation of the fluorescent microarray analyzer (5) is more easily.
If the concentration of the sample is lower and the emitting fluorescence is weaker, detection time can be extended, as shown in
In addition, if desired, image data as shown in
As mentioned above, spectrophotometer is used as the signal detector of the fluorescent microarray analyzer of the present invention. There is no need to set a filter and more accurate signals of fluorescence are obtained. Furthermore, the signal intensity of each sample comes directly from signals detected by the spectrophotometer so that no errors arise as what happened in process of converting an electrical signal into image data in the conventional biochip. Also, it allows doing a real-time analysis without scanning all samples on the biochip
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US6664061 *||Aug 9, 2001||Dec 16, 2003||Amersham Biosciences Ab||Use and evaluation of a [2+2] photoaddition in immobilization of oligonucleotides on a three-dimensional hydrogel matrix|
|US20040072722 *||Jan 2, 2003||Apr 15, 2004||Kornblith Paul L.||Methods for assessing efficacy of chemotherapeutic agents|
|US20040265905 *||Jun 26, 2003||Dec 30, 2004||Samuel Chen||Color detection using spectroscopic imaging and processing in random array of microspheres|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US7528374||Mar 3, 2006||May 5, 2009||Vidar Systems Corporation||Sensing apparatus having optical assembly that collimates emitted light for detection|
|US7858382||May 27, 2005||Dec 28, 2010||Vidar Systems Corporation||Sensing apparatus having rotating optical assembly|
|US8449842||Mar 11, 2010||May 28, 2013||Thermo Scientific Portable Analytical Instruments Inc.||Molecular reader|
|US20060269450 *||May 27, 2005||Nov 30, 2006||Kim Yong M||Sensing apparatus having rotating optical assembly|
|US20100151474 *||Dec 22, 2009||Jun 17, 2010||Vladimir Nikolaevich Afanasyev||Multifunctional Device For Diagnostics and Method For Testing Biological Objects|
|US20110022324 *||Mar 11, 2010||Jan 27, 2011||Knopp Kevin J||Molecular reader|
|U.S. Classification||356/317, 250/458.1|
|Cooperative Classification||G01N21/6452, G01N2021/6417|
|Feb 13, 2004||AS||Assignment|
Owner name: KAIWOOD TECHNOLOGY CO., LTD., TAIWAN
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:WANG, JIANN-HUA;CHEN, HUI-JU;WU, TZU-CHIANG;AND OTHERS;REEL/FRAME:015097/0452
Effective date: 20040102
|Sep 7, 2009||FPAY||Fee payment|
Year of fee payment: 4
|Dec 20, 2013||REMI||Maintenance fee reminder mailed|
|May 9, 2014||LAPS||Lapse for failure to pay maintenance fees|
|Jul 1, 2014||FP||Expired due to failure to pay maintenance fee|
Effective date: 20140509